3-alkyl fentanyl analogues: Structure-activity-relationship study
3-alkil analozi fentanila - studija odnosa strukture i aktivnost
Нема приказа
Аутори
Vučković, Sonja M.Savić-Vujović, Katarina
Srebro, Dragana
Ivanović, Milovan
Došen-Mićović, Ljiljana
Stojanović, Radan
Prostran, Milica
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. Analgesic activity was assessed by tail-immersion test in rats. Results. The relative potency was: (±)cis-3-methyl fentanyl (8) gt (±)trans-3-methyl fentanyl (2) $ (±)cis-3-ethyl fentanyl (1.5) gt fentanyl (1) $ (±)trans-3-ethyl fentanyl (0.9) gt (±)cis-3-butyl fentanyl (0.064) $ (±)trans-3-butyl fentanyl (0.035) gt (±)cis-3-benzyl fentanyl (0.008) $ (±)trans-3-benzyl fentanyl (0.0055). (±)Cis-3-iso-propyl fentanyl, and (±)cis-3-phenethyl fentanyl are inactive in doses up to 5 mg/kg. The du...ration of action (ED99) was: (±)cis-3-methyl fentanyl (90 min) gt (±)trans-3-methyl fentanyl (40 min) # (±)cis-3-ethyl fentanyl (60 min) $ (±)trans-3-ethyl fentanyl (40 min) # fentanyl (50 min) = (±)cis-3-butyl fentanyl (50 min) = (±)trans-3-butyl fentanyl (50 min) = (±)cis-3-benzyl fentanyl (50 min) = (±)trans-3-benzyl fentanyl (50 min). Symbols gt and lt denotes p lt 0.05. Conclusion. It is concluded that the analgesic potency of 3-alkyl fentanyl analogues is influenced by the steric factor (voluminosity of the group at the position 3 of the piperidine ring and the cis/trans isomerism). Otherwise, with the exception of 3-methyl fentanyl, the duration of action of 3-alkyl fentanyl analogues is not significantly affected by the stereochemistry.
Uvod. Fentanil pripada grupi sintetskih opioidnih analgetika, 4-anilidopiperidina. Karakteriše ga visoka potentnost, brz početak i kratko trajanje dejstva. Do sada je sintetisan veliki broj analoga fentanila, kako u cilju određivanja odnosa strukture i farmakološke aktivnosti, tako i u cilju pronalaženja novog klinički korisnog analgetika. Cilj rada. U studiji su ispitivana analgetska dejstva novosintetisanih 3-alkil analoga fentanila i poređena sa fentanilom. Metod rada. Merenje analgetskog dejstva ispitivanih jedinjenja vršeno je uz pomoć testa potapanja repa pacova u toplu vodu. Rezultati. Relativna jačina jedinjenja iznosila je: (±)cis-3-metil fentanil (8) gt (±)trans-3-metil fentanil (2) $ (±)cis-3-etil fentanil (1,5) gt fentanil (1) $ (±)trans-3-etil fentanil (0,9) gt (±)cis-3-butil fentanil (0,064) $ (±)trans-3-butil fentanil (0,035) gt (±)cis-3-benzil fentanil (0,008) $ (±)trans-3-benzil fentanil (0,0055). (±)Cis-3-izopropil fentanil i (±)cis-3-fenetil fentanil nisu isp...oljili dejstvo u dozama do 5 mg/kg. Dužina dejstva (ED99) iznosila je: (±)cis-3-metil fentanil (90 min) gt (±)trans-3-metil fentanil (40 min) # (±)cis-3-etil fentanil (60 min) $ (±)trans-3-etil fentanil (40 min) # fentanil (50 min) = (±)cis-3-butil fentanil (50 min) = (±)trans-3-butil fentanil (50 min) = (±)cis-3-benzil fentanil (50 min) = (±)trans-3-benzil fentanil (50 min). Oznake gt i lt označavaju P lt 0.05. Zaključak Zaključeno je da na analgetsku jačinu 3-alkil analoga fentanila utiče sterni faktor (voluminoznost grupe na položaju 3 piperidinskog prstena i cis/trans izomerizam). Inače, uz izuzetak 3-metil fentanila, stereohemija ne utiče značajno na dužinu dejstva 3-alkil analoga fentanila.
Кључне речи:
fentanyl / analogues / structure-activity-relationship(SAR) / analgesic activity / fentanil / analozi / struktura / analgetska aktivnostИзвор:
Engrami, 2012, 34, 3, 15-26Финансирање / пројекти:
- Базична и клиничко-фармаколошка истраживања механизама дејства и интеракција лекова у нервном и кардиоваскуларном систему (RS-MESTD-Basic Research (BR or ON)-175023)
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Vučković, Sonja M. AU - Savić-Vujović, Katarina AU - Srebro, Dragana AU - Ivanović, Milovan AU - Došen-Mićović, Ljiljana AU - Stojanović, Radan AU - Prostran, Milica PY - 2012 UR - https://cherry.chem.bg.ac.rs/handle/123456789/140 AB - Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. Analgesic activity was assessed by tail-immersion test in rats. Results. The relative potency was: (±)cis-3-methyl fentanyl (8) gt (±)trans-3-methyl fentanyl (2) $ (±)cis-3-ethyl fentanyl (1.5) gt fentanyl (1) $ (±)trans-3-ethyl fentanyl (0.9) gt (±)cis-3-butyl fentanyl (0.064) $ (±)trans-3-butyl fentanyl (0.035) gt (±)cis-3-benzyl fentanyl (0.008) $ (±)trans-3-benzyl fentanyl (0.0055). (±)Cis-3-iso-propyl fentanyl, and (±)cis-3-phenethyl fentanyl are inactive in doses up to 5 mg/kg. The duration of action (ED99) was: (±)cis-3-methyl fentanyl (90 min) gt (±)trans-3-methyl fentanyl (40 min) # (±)cis-3-ethyl fentanyl (60 min) $ (±)trans-3-ethyl fentanyl (40 min) # fentanyl (50 min) = (±)cis-3-butyl fentanyl (50 min) = (±)trans-3-butyl fentanyl (50 min) = (±)cis-3-benzyl fentanyl (50 min) = (±)trans-3-benzyl fentanyl (50 min). Symbols gt and lt denotes p lt 0.05. Conclusion. It is concluded that the analgesic potency of 3-alkyl fentanyl analogues is influenced by the steric factor (voluminosity of the group at the position 3 of the piperidine ring and the cis/trans isomerism). Otherwise, with the exception of 3-methyl fentanyl, the duration of action of 3-alkyl fentanyl analogues is not significantly affected by the stereochemistry. AB - Uvod. Fentanil pripada grupi sintetskih opioidnih analgetika, 4-anilidopiperidina. Karakteriše ga visoka potentnost, brz početak i kratko trajanje dejstva. Do sada je sintetisan veliki broj analoga fentanila, kako u cilju određivanja odnosa strukture i farmakološke aktivnosti, tako i u cilju pronalaženja novog klinički korisnog analgetika. Cilj rada. U studiji su ispitivana analgetska dejstva novosintetisanih 3-alkil analoga fentanila i poređena sa fentanilom. Metod rada. Merenje analgetskog dejstva ispitivanih jedinjenja vršeno je uz pomoć testa potapanja repa pacova u toplu vodu. Rezultati. Relativna jačina jedinjenja iznosila je: (±)cis-3-metil fentanil (8) gt (±)trans-3-metil fentanil (2) $ (±)cis-3-etil fentanil (1,5) gt fentanil (1) $ (±)trans-3-etil fentanil (0,9) gt (±)cis-3-butil fentanil (0,064) $ (±)trans-3-butil fentanil (0,035) gt (±)cis-3-benzil fentanil (0,008) $ (±)trans-3-benzil fentanil (0,0055). (±)Cis-3-izopropil fentanil i (±)cis-3-fenetil fentanil nisu ispoljili dejstvo u dozama do 5 mg/kg. Dužina dejstva (ED99) iznosila je: (±)cis-3-metil fentanil (90 min) gt (±)trans-3-metil fentanil (40 min) # (±)cis-3-etil fentanil (60 min) $ (±)trans-3-etil fentanil (40 min) # fentanil (50 min) = (±)cis-3-butil fentanil (50 min) = (±)trans-3-butil fentanil (50 min) = (±)cis-3-benzil fentanil (50 min) = (±)trans-3-benzil fentanil (50 min). Oznake gt i lt označavaju P lt 0.05. Zaključak Zaključeno je da na analgetsku jačinu 3-alkil analoga fentanila utiče sterni faktor (voluminoznost grupe na položaju 3 piperidinskog prstena i cis/trans izomerizam). Inače, uz izuzetak 3-metil fentanila, stereohemija ne utiče značajno na dužinu dejstva 3-alkil analoga fentanila. T2 - Engrami T1 - 3-alkyl fentanyl analogues: Structure-activity-relationship study T1 - 3-alkil analozi fentanila - studija odnosa strukture i aktivnost VL - 34 IS - 3 SP - 15 EP - 26 UR - https://hdl.handle.net/21.15107/rcub_cherry_140 ER -
@article{ author = "Vučković, Sonja M. and Savić-Vujović, Katarina and Srebro, Dragana and Ivanović, Milovan and Došen-Mićović, Ljiljana and Stojanović, Radan and Prostran, Milica", year = "2012", abstract = "Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. Analgesic activity was assessed by tail-immersion test in rats. Results. The relative potency was: (±)cis-3-methyl fentanyl (8) gt (±)trans-3-methyl fentanyl (2) $ (±)cis-3-ethyl fentanyl (1.5) gt fentanyl (1) $ (±)trans-3-ethyl fentanyl (0.9) gt (±)cis-3-butyl fentanyl (0.064) $ (±)trans-3-butyl fentanyl (0.035) gt (±)cis-3-benzyl fentanyl (0.008) $ (±)trans-3-benzyl fentanyl (0.0055). (±)Cis-3-iso-propyl fentanyl, and (±)cis-3-phenethyl fentanyl are inactive in doses up to 5 mg/kg. The duration of action (ED99) was: (±)cis-3-methyl fentanyl (90 min) gt (±)trans-3-methyl fentanyl (40 min) # (±)cis-3-ethyl fentanyl (60 min) $ (±)trans-3-ethyl fentanyl (40 min) # fentanyl (50 min) = (±)cis-3-butyl fentanyl (50 min) = (±)trans-3-butyl fentanyl (50 min) = (±)cis-3-benzyl fentanyl (50 min) = (±)trans-3-benzyl fentanyl (50 min). Symbols gt and lt denotes p lt 0.05. Conclusion. It is concluded that the analgesic potency of 3-alkyl fentanyl analogues is influenced by the steric factor (voluminosity of the group at the position 3 of the piperidine ring and the cis/trans isomerism). Otherwise, with the exception of 3-methyl fentanyl, the duration of action of 3-alkyl fentanyl analogues is not significantly affected by the stereochemistry., Uvod. Fentanil pripada grupi sintetskih opioidnih analgetika, 4-anilidopiperidina. Karakteriše ga visoka potentnost, brz početak i kratko trajanje dejstva. Do sada je sintetisan veliki broj analoga fentanila, kako u cilju određivanja odnosa strukture i farmakološke aktivnosti, tako i u cilju pronalaženja novog klinički korisnog analgetika. Cilj rada. U studiji su ispitivana analgetska dejstva novosintetisanih 3-alkil analoga fentanila i poređena sa fentanilom. Metod rada. Merenje analgetskog dejstva ispitivanih jedinjenja vršeno je uz pomoć testa potapanja repa pacova u toplu vodu. Rezultati. Relativna jačina jedinjenja iznosila je: (±)cis-3-metil fentanil (8) gt (±)trans-3-metil fentanil (2) $ (±)cis-3-etil fentanil (1,5) gt fentanil (1) $ (±)trans-3-etil fentanil (0,9) gt (±)cis-3-butil fentanil (0,064) $ (±)trans-3-butil fentanil (0,035) gt (±)cis-3-benzil fentanil (0,008) $ (±)trans-3-benzil fentanil (0,0055). (±)Cis-3-izopropil fentanil i (±)cis-3-fenetil fentanil nisu ispoljili dejstvo u dozama do 5 mg/kg. Dužina dejstva (ED99) iznosila je: (±)cis-3-metil fentanil (90 min) gt (±)trans-3-metil fentanil (40 min) # (±)cis-3-etil fentanil (60 min) $ (±)trans-3-etil fentanil (40 min) # fentanil (50 min) = (±)cis-3-butil fentanil (50 min) = (±)trans-3-butil fentanil (50 min) = (±)cis-3-benzil fentanil (50 min) = (±)trans-3-benzil fentanil (50 min). Oznake gt i lt označavaju P lt 0.05. Zaključak Zaključeno je da na analgetsku jačinu 3-alkil analoga fentanila utiče sterni faktor (voluminoznost grupe na položaju 3 piperidinskog prstena i cis/trans izomerizam). Inače, uz izuzetak 3-metil fentanila, stereohemija ne utiče značajno na dužinu dejstva 3-alkil analoga fentanila.", journal = "Engrami", title = "3-alkyl fentanyl analogues: Structure-activity-relationship study, 3-alkil analozi fentanila - studija odnosa strukture i aktivnost", volume = "34", number = "3", pages = "15-26", url = "https://hdl.handle.net/21.15107/rcub_cherry_140" }
Vučković, S. M., Savić-Vujović, K., Srebro, D., Ivanović, M., Došen-Mićović, L., Stojanović, R.,& Prostran, M.. (2012). 3-alkyl fentanyl analogues: Structure-activity-relationship study. in Engrami, 34(3), 15-26. https://hdl.handle.net/21.15107/rcub_cherry_140
Vučković SM, Savić-Vujović K, Srebro D, Ivanović M, Došen-Mićović L, Stojanović R, Prostran M. 3-alkyl fentanyl analogues: Structure-activity-relationship study. in Engrami. 2012;34(3):15-26. https://hdl.handle.net/21.15107/rcub_cherry_140 .
Vučković, Sonja M., Savić-Vujović, Katarina, Srebro, Dragana, Ivanović, Milovan, Došen-Mićović, Ljiljana, Stojanović, Radan, Prostran, Milica, "3-alkyl fentanyl analogues: Structure-activity-relationship study" in Engrami, 34, no. 3 (2012):15-26, https://hdl.handle.net/21.15107/rcub_cherry_140 .